Ceftriaxone alleviates early brain injury after subarachnoid hemorrhage by increasing excitatory amino acid transporter 2 expression via the PI3K/Akt/NF-κB signaling pathway.

Abstract Early brain injury (EBI) after subarachnoid hemorrhage (SAH) is characterized by a reduction in excitatory amino acid transporter 2 (EAAT2) expression and severe amino acid excitotoxicity. The aim of this study was to explore the neuroprotective effect of ceftriaxone (CEF), a potent compound that up-regulates EAAT2, against EBI and the potential mechanisms using in vitro experiments and a rat model of SAH. Intracisternal treatment with CEF significantly improved neurological outcomes and alleviated extracellular glutamate accumulation after SAH. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining and Western blot analysis of cleaved caspase 3 showed that CEF decreased hippocampal neuronal apoptosis following SAH. Immunofluorescent staining and Western blotting revealed that CEF significantly reversed the down-regulation of EAAT2 expression following SAH. In Morris water maze (MWM) tests, CEF remarkably ameliorated the SAH-induced cognitive dysfunction in spatial learning memory and reference memory. CEF promoted the nuclear translocation of p65 as well as the activation of Akt in hippocampal astrocytes in vitro and in vivo . These findings suggest that CEF may exert significant protective effects against EBI following SAH by modulating the PI3K/Akt/NF-κB signaling pathway.